I would like to express my appreciation to Secretary Thompson and the HHS for their foresight in preparing this pandemic preparedness plan. This is a much needed step towards protecting the world from an incipient pandemic. In particular, a renewed focus on basic science research is vital if we are to meet this challenge.
I would like to make a brief comment on Annex 10: Pandemic Influenza Research. The goals for this section are laudable and I do not disagree with any of the research priorities laid out there. However, I feel the area of pathogenesis in humans has been relatively undervalued in the prioritization. Although influenza is one of the leading causes of death in the world, the primary viral infection is rarely the direct cause of mortality. Instead, infected persons die of cardiac disease (usually patients with pre-existing co-morbidities) or succumb to secondary bacterial pneumonia. Around 25% of all mortality during a typical influenza season is due secondary bacterial infections. This association is even stronger during pandemic influenza, where around 70% of influenza cases are complicated by bacterial co-infections. Thus, it can be predicted that the virulent influenza virus strains that are most likely to cause the next pandemic, or to be utilized as agents of bioterrorism, would achieve much of their impact through secondary infections. Despite this association being appreciated since 1803 and being the focus of the majority of research following the 1918 pandemic, little is known about the pathogenesis of either cardiac death or secondary bacterial infections following influenza. A clearer understanding of the pathogenesis that underlies these interactions will provide targets for drug or vaccine-based interventions. For instance, it could be hypothesized that the statin class of drugs, a widely available and inexpensive set of compounds that have anti-inflammatory activity, could ameliorate the cardiac complications of influenza reducing the death toll during a pandemic. However, no basic research into this area has been attempted.
Thus, I would respectfully suggest that the following Goal and Priority Actions be added to Annex 10 under the Basic Virology and Molecular Virology section:
Goal: To understand the mechanisms by which influenza viruses predispose to bacterial infections.
Goal: To understand the mechanisms by which influenza viruses contribute to pulmonary, cardiac, and circulatory deaths.
Priority Actions:
- Conduct studies to determine the mechanisms that predispose to bacterial infections during influenza so that vaccine and drug based interventions can be developed.
- Determine the contribution of specific viral virulence factors to secondary bacterial infections to aid in identification of viruses or gene segments with the potential to contribute to epidemic and pandemic mortality.
- Conduct studies to determine the mechanisms by which influenza exacerbates pre-existing pulmonary or cardiac disease.